Practical Large-Scale Preparation of (R)-Rolipram Using Chiral Nickel Catalyst

Abstract Antidepressant drug (R)-rolipram was readily prepared on a large scale from isovanilline via a succinct route. The key reaction was carried out using a 1 mol% loading of nickel(II)-bis[(S,S)-N,N′-dibenzylcyclohexane-1,2-diamine]Br2 complex as the catalyst. The ee% could reach to 99%, and the catalyst could be recovered and used in the next reaction cycle with high ee%.